桃红四物汤加味治疗药源性闭经80例

[目的]观察桃红四物汤加味治疗药源性闭经疗效。[方法]对80例服用抗精神病药物导致月经中断达3个月以上（用药前月经规律）的女性精神病患者,使用桃红四物汤（药用桃仁、红花、当归、川芎、生地、赤芍）,随证加减。1剂/d,水煎服,5～7d为1疗程,治疗3个疗程,随访半年判定疗效。[结果]痊愈34例,显效36例,无效10例,总有效率87.50%。[结论]桃红四物汤加味治疗抗精神病药物治疗精神疾病的同时引起女性药源性闭经疗效满意。     

某社区精神卫生中心2012～2014年抗抑郁药物的应用分析

目的：分析成都高新区社区精神卫生中心2012～2014年抗抑郁药物的使用情况及发展趋势,为临床合理用药提供参考。方法：回顾性统计、分析该中心2012～2014年抗抑郁药物的销售金额、用药频度（DDDs）及日均费用（DDC）。结果：该中心抗抑郁药物的销售金额逐年增长;5-羟色胺再摄取抑制剂（SSRIs）销售金额和用药频度均占据最主要地位。结论：SSRIs成为该中心抑郁病治疗的主要药物,该中心该类药物的应用状况与国内外总体用药情况基本相符。     

Preclinical pharmacology of F-98214-TA, a novel potent serotonin and norepinephrine uptake inhibitor with antidepressant and anxiolytic properties

Rationale Serotonin (5-HT) and norepinephrine (NE) re-uptake inhibitors (SNRIs) have been proposed to have a higher efficacy and/or faster onset of action than previously available antidepressants. Objectives We examined in biochemical, electrophysiological and behavioural assays the antidepressant properties of (S)-(−)-4-[(3-fluorophenoxy)-phenyl]methyl-piperidine (F-98214-TA), a compound that displays very high affinity for 5-HT and NE transporters. Results F-98214-TA potently inhibited the uptake of both 5-HT and NE into rat brain synaptosomes (IC₅₀=1.9 and 11.2 nM, respectively) and decreased the electrical activity of dorsal raphe serotonergic neurones (ED₅₀=530.3 μg/kg i.v.), an effect completely abolished by the 5-HT_1A antagonist WAY100,635. In acute behavioural assays in mice, the orally administered compound potentiated the 5-hydroxy-tryptophan (5-HTP)-induced syndrome [minimal effective dose (MED)=10 mg/kg], antagonized the hypothermia induced by a high dose of apomorphine (ED₅₀=2 mg/kg) and reduced the immobility in the tail suspension test (MED=10 mg/kg). Moreover, it also decreased the immobility in the forced swimming test in mice and rats (30 mg/kg, p.o.). Chronic administration of F-98214-TA (14 days, 30 mg kg⁻¹ day⁻¹, p.o.) attenuated the hyperactivity induced by olfactory bulbectomy in rats, confirming its antidepressant-like properties. Interestingly, the same dosage regimen significantly increased the social interaction time in rats, suggesting an additional potential anxiolytic activity. In most assays the compound was more potent than fluoxetine, venlafaxine and desipramine. Conclusions F-98214-TA is a novel SNRI that displays greater potency than other reference antidepressants in animal models predictive of antidepressant and anxiolytic activities. A preliminary report of this work was presented at the 30th Annual Meeting of the Society for Neuroscience, New Orleans, LA, 2000.     

The four-plates test–retest paradigm to discriminate anxiolytic effects

Rationale Animal models of anxiety such as the four-plates test (FPT) enable the detection of an anxiolytic effect not only of benzodiazepines (BZDs) but also of other non-BZD anxiolytic compounds such as the antidepressants paroxetine and venlafaxine. Retesting mice in animal models of anxiety markedly alters the behavioural profile of various drugs.Objectives The aim of this study was first to investigate the function of GABA_A/BZD receptor and passive avoidance acquisition in the FPT test–retest. The second aim of this study was to evaluate the capacity of the FPT to discriminate BZDs from other non-BZD anxiolytics in experienced mice.Methods The FPT was performed in naive and experienced mice (submitted to the test 24 h previously). The drugs studied were two BZDs, diazepam (1 mg/kg) and alprazolam (0.25 mg/kg); flumazenil, a GABA_A receptor antagonist (8 mg/kg); atropine sulphate, a muscarinic cholinergic receptor antagonist (4 mg/kg) known for its amnesic properties; paroxetine, a selective serotonin reuptake inhibitor (4 and 8 mg/kg); venlafaxine, a serotonin and noradrenalin reuptake inhibitor (4 and 16 mg/kg); and DOI, a 5-HT_2A agonist (1 mg/kg).Results Our results reveal an increase of anxiety (decrease of punished passages) in saline-experienced mice. Diazepam, alprazolam, paroxetine and venlafaxine did not prevent the increase in anxiety during retest, revealing a passive avoidance acquisition. Flumazenil did not modify the anxiogenic-like behaviour of experienced mice. In contrast, atropine seems to oppose the increase of anxiety; however, its effect is weak and disputable. DOI was the only anxiolytic compound able to oppose the decrease of punished passages of experienced mice.Conclusion Anxiogenic behaviour on retesting indicates aversive learning. The protocol test–retest is unable to discriminate between the anxiolytic effect of BZDs from that of paroxetine or venlafaxine. However, this modified model may constitute a new tool to investigate other neural pathways implicated in anxiety.     

Antidepressant-like effects of agomelatine,melatonin and the NK<Subscript>1</Subscript> receptor antagonist GR205171 in impulsive-related behaviour in rats

Rationale Substance P receptor [neurokinin₁ (NK₁-R)] antagonists and melatonin_1/2 receptor (MT_1/2-R) agonists have been claimed to be potential antidepressants (ADs). In animals, these compounds are active in validated models responsive to ADs, such as forced swimming test and chronic mild stress paradigms. Classical AD drugs are also known to be effective in pathologies characterized by an impulse control deficiency. In line with this clinical observation, previous studies demonstrated that classical ADs increased the capacity to wait for food reward in rats subjected to a paradigm aimed at assessing impulsive-related behaviour. Objectives This study was conducted to investigate the effects of two MT_1/2-R agonists, melatonin and agomelatine, and a NK₁-R antagonist, GR205171, on tolerance to delay of food reward in rats. Methods Fasting rats were trained in a T-maze and allowed to choose between two magnitudes of reward: immediate but small reward (two pellets) vs 25-s delayed but large reward (ten pellets). Under this alternative, vehicle-injected rats selected the large-but-delayed reinforcer in less than 40% of the trials. Results Like the established ADs clomipramine (8 mg kg⁻¹, i.p.) and fluvoxamine (4 mg kg⁻¹, i.p.), melatonin (3 and 10 mg kg⁻¹, i.p.), agomelatine (10 and 30 mg kg⁻¹, i.p.) and GR205171 (30 mg kg⁻¹ but not 10 mg kg⁻¹, s.c.) significantly increased the number of choices of the large-but-delayed reward. The effect of melatonin (3 mg kg⁻¹, i.p.) was not counteracted by the MT_1/2-R antagonist S22153 (40 mg kg⁻¹, i.p.) that exerted no effect on its own. Conclusion These results suggest that MT_1/2-R agonists and NK₁-R antagonists enhance rats' tolerance to delay of gratification, an effect which may reflect their ability to improve impulse control. Further investigations are necessary to clarify the neurobiological mechanisms responsible for this effect.     

Effects of chronic selective serotonin reuptake inhibitors on 8-OH-DPAT-induced facilitation of ejaculation in rats: comparison of fluvoxamine and paroxetine

Rationale Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) can delay ejaculation in humans, but the extent of this effect differs between SSRIs. The involvement of 5-HT_1A receptors is likely, since 5-HT_1A receptor agonists accelerate ejaculation and chronic SSRI treatment is thought to desensitize 5-HT_1A receptors.Objectives This study was conducted to examine the effects of chronic pretreatment with the SSRIs fluvoxamine and paroxetine on the facilitation of ejaculation induced by the 5-HT_1A receptor agonist 8-OH-DPAT.Methods Sexually experienced Wistar rats with normal ejaculatory behavior were treated for 22 days with vehicle, fluvoxamine (30 mg/kg/day), or paroxetine (10 or 20 mg/kg/day, p.o.). On day 22, rats received a challenge with saline or 8-OH-DPAT (0.4 mg/kg, s.c.). Sexual behavior was tested on days 1, 8, 15, and 22 of the SSRI-treatment.Results Treatment with both doses of paroxetine, but not fluvoxamine, delayed ejaculation. 8-OH-DPAT strongly accelerated ejaculation under vehicle conditions. Pretreatment with paroxetine reduced the effects of 8-OH-DPAT on ejaculation in a dose-dependent manner and more strongly than fluvoxamine.Conclusions SSRIs affect 5-HT_1A receptors involved in ejaculation. The degree to which this occurs, with paroxetine exerting a stronger effect than fluvoxamine, might determine the extent of SSRI-induced delayed ejaculation.     

Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: a 6-month randomized controlled trial

Rationale There is a need for new pharmacological treatments for generalized social anxiety disorder (GSAD), which is a common, often disabling condition.Objective To compare the efficacy and safety over 6 months duration of two dose ranges of venlafaxine extended-release (ER) with placebo in patients with GSAD.Method Twenty-eight-week, double-blind, multi-center study in 386 adult outpatients with DSM-IV GSAD. Patients were randomized to placebo, venlafaxine ER fixed low dose (75 mg/day), or venlafaxine ER flexible higher dose (150–225 mg/day). Primary efficacy variable was change on the Liebowitz Social Anxiety Scale (LSAS). Secondary efficacy variables included, among others, the proportion of responders on the CGI Global Improvement Item (score 1 or 2), and the proportion of remitters (defined as an LSAS score of 30).Results Improvement on the LSAS was greater with venlafaxine ER (at 75 mg/day or 150–225 mg/day) than placebo, and was sustained throughout the 6-month trial. Of patients receiving venlafaxine ER (at any dose), 58% responded to treatment compared to 33% of those receiving placebo (P<0.001); corresponding remission rates were 31% and 16% (P<0.01). There were no differences in outcome according to venlafaxine ER dosage.Conclusions Venlafaxine ER was effective in the treatment of GSAD. The comparable efficacy at low and higher doses may indicate that norepinephrine reuptake blockade does not contribute to therapeutic effect in GSAD. This hypothesis should be tested using agents with specific actions on norepinephrine reuptake blockade.     

四种新型抗抑郁药治疗抑郁症的成本-效果评价

目的评价4种新型抗抑郁药物治疗抑郁症的成本-效果。方法将104例符合抑郁症首次发病的患者随机分为4组,分别给予度洛西汀胶囊、文拉法辛缓释胶囊、米氮平片、艾司西酞普兰片。疗效采用17项汉密尔顿抑郁量表（HAMD17）。运用成本-效果法进行分析。结果 4组有效率分别为73.08%、69.23%、69.23%、73.08%（P〉0.05）,成本分别为768.6元、562.8元、751.2元、751.8元,痊愈的成本-效果比为13.32、11.26、12.36、13.97;有效性的成本-效果比为10.51、8.13、8.25、10.28。结论文拉法辛缓释胶囊组治疗抑郁症成本-效果比更优。     

氢溴酸沃替西汀合成工艺改进

改进氢溴酸沃替西汀的合成工艺,以提高收率,简化处理过程。以2,4-二甲基苯硫酚和邻氯硝基苯为起始原料,经亲核取代、还原、缩合、成盐制得目标化合物。目标化合物经过1H-NMR,MS得到确证。该路线原料易得,后处理简单,反应条件温和,无需任何催化剂、缚酸剂。以2,4-二甲基苯硫酚计,总收率为57.3%,适合工业化生产。